Pharmaceutical Development and Technology最新文献_第6页

Applications of therapeutic deep eutectic solvents (THEDESs) as antimicrobial and anticancer agents. 治疗性深共晶溶剂（THEDESs）作为抗菌剂和抗癌剂的应用。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1080/10837450.2024.2421786

Hala Bakr El-Nassan

引用次数: 0

Formulation and evaluation of ibrutinib-loaded glycyrrhizic acid conjugated ovalbumin nanoparticles and ibrutinib-glycyrrhizic acid complex for improved oral bioavailability. 负载依鲁替尼的甘草酸共轭卵清蛋白纳米颗粒和依鲁替尼-甘草酸配合物改善口服生物利用度的配方和评价。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-12-06 DOI: 10.1080/10837450.2024.2436190

Prateeksha Prakash Kamath, Pragathi Devanand Bangera, Divya Dhatri Kara, Rajeshwari Roychowdhury, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand

{"title":"Formulation and evaluation of ibrutinib-loaded glycyrrhizic acid conjugated ovalbumin nanoparticles and ibrutinib-glycyrrhizic acid complex for improved oral bioavailability.","authors":"Prateeksha Prakash Kamath, Pragathi Devanand Bangera, Divya Dhatri Kara, Rajeshwari Roychowdhury, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand","doi":"10.1080/10837450.2024.2436190","DOIUrl":"10.1080/10837450.2024.2436190","url":null,"abstract":"The study aimed at enhancing the oral bioavailability of the BCS class 2 drug Ibrutinib (IBR), which exhibits low solubility (0.002 mg/mL) and high permeability (3.9% oral bioavailability). This was achieved through the formulation and evaluation of Ibrutinib-loaded Glycyrrhizic acid conjugated egg ovalbumin nanoparticles (IBR-GA-EA NPs) and Ibrutinib-Glycyrrhizic acid complex (IBR-GA-COMP). The formulation of Ibrutinib-Glycyrrhizic acid complex aimed to enhance the oral bioavailability of Ibrutinib. Lyophilized Ibrutinib-Glycyrrhizic acid complex was prepared and characterized through various studies including DSC, FTIR, in vitro release, and in vivo pharmacokinetics studies. DSC and FTIR confirmed successful formulation development. The nanoparticles exhibited spherical morphology with favourable characteristics: particle size of 194.10 nm, PDI of 0.22, and zeta potential of -33.96 mV. Encapsulation efficiency was 82.88%. In vitro release study displayed major improvement in drug release pattern compared to the free drug suspension. In vivo pharmacokinetic studies demonstrated 3.21-fold and 3.41-fold increase in the oral bioavailability of IBR-GA-EA NPs and IBR-GA-COMP, respectively, compared to IBR suspension alone. The formulated IBR-GA-EA NPs and IBR-GA-COMP are promising drug delivery methods as they successfully improve the solubility and oral bioavailability of Ibrutinib.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1185-1198"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic characterization of fast dissolving PVP-I powder with multipolymer approaches and investigation on their molecular interaction. 采用多聚物方法快速溶解 PVP-I 粉末的机理特征及其分子相互作用研究。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-21 DOI: 10.1080/10837450.2024.2428772

Maytawee Wutthichokmongkhonkul, Rutthapol Sritharadol, Teerapol Srichana

{"title":"Mechanistic characterization of fast dissolving PVP-I powder with multipolymer approaches and investigation on their molecular interaction.","authors":"Maytawee Wutthichokmongkhonkul, Rutthapol Sritharadol, Teerapol Srichana","doi":"10.1080/10837450.2024.2428772","DOIUrl":"10.1080/10837450.2024.2428772","url":null,"abstract":"Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol-polyvinyl alcohol copolymer (PEG-PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG-PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG-PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG-PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10-12%), and the antimicrobial activity proved effective against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1162-1174"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro skin permeation of flavonoid esters enzymatically derived from natural oils: release mechanism from gel emulsion, stability, and dermatological compatibility. 从天然油中酶解提取的类黄酮酯的体外皮肤渗透性：凝胶乳液的释放机制、稳定性和皮肤相容性。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-09 DOI: 10.1080/10837450.2024.2424977

Ana Milivojević, Marija Ćorović, Anja Petrov Ivanković, Milica Simović, Katarina Banjanac, Rada Pjanović, Dejan Bezbradica

{"title":"In vitro skin permeation of flavonoid esters enzymatically derived from natural oils: release mechanism from gel emulsion, stability, and dermatological compatibility.","authors":"Ana Milivojević, Marija Ćorović, Anja Petrov Ivanković, Milica Simović, Katarina Banjanac, Rada Pjanović, Dejan Bezbradica","doi":"10.1080/10837450.2024.2424977","DOIUrl":"10.1080/10837450.2024.2424977","url":null,"abstract":"Due to their broad spectrum of biological activities and attractive pharmacological properties, flavonoids are very promising molecules for application in skin care products. In this study, phloridzin and naringin medium- and long-chain fatty acid esters were enzymatically synthesized in reaction with natural oils (coconut and linseed oil) and in vitro transdermal delivery of synthesized esters through artificial Strat-M® membrane was investigated. Experimental results were succesfully fitted using Peppas and Sahlin model which includes the lag phase. Release kinetics of all examined flavonoid esters from gel emulsions through the membrane depended on both diffusion and polymer relaxation effect (0.5<n < 1). The estimated effective diffusion coefficients ranged from 0.168·10-8 to 6.149·10-8 cm2 s-1 for phloridzin esters and from 0.116·10-8 to 4.210·10-8 cm2 s-1 for naringin esters. The effective diffusion coefficients decreased with the increase in ester molecular weight indicating the size-dependent diffusion. All formulation showed good stability, excellent hydration effect, and excellent dermatological compatibility without irritating effect. It can be concluded that gel emulsions with a mixture of flavonoid esters enzymatically synthesized in reaction with vegetable oils can be effectively topically applied as a skin care products.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1121-1132"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 更正。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-18 DOI: 10.1080/10837450.2024.2428508

引用次数: 0

Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety. 美洛昔康-氨基酸盐/离子对复合物，具有更高的溶解度、溶解性和胃安全性。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-10-24 DOI: 10.1080/10837450.2024.2417766

Hamdy Abdelkader, Adel Al Fatease, Zeinab Fathalla, Mai E Shoman, Heba A Abou-Taleb

{"title":"Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety.","authors":"Hamdy Abdelkader, Adel Al Fatease, Zeinab Fathalla, Mai E Shoman, Heba A Abou-Taleb","doi":"10.1080/10837450.2024.2417766","DOIUrl":"10.1080/10837450.2024.2417766","url":null,"abstract":"Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible, and low-molecular-weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset, and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent in vitro dissolution, docking, DSC, FTIR, XRD, solubility, and gastric ulcer formation studies. Docking indicated ion pair/salt formation between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000-fold and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1075-1083"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ionic liquids and their potential use in development and improvement of drug delivery systems: evidence of their tendency to promote drug accumulation in the brain. 离子液体及其在开发和改进给药系统中的潜在用途：有证据表明离子液体有促进药物在大脑中蓄积的倾向。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-10-18 DOI: 10.1080/10837450.2024.2417004

William Eades, Shayan Abdolmohammadpourbonab, Linh Dinh, Bingfang Yan

{"title":"Ionic liquids and their potential use in development and improvement of drug delivery systems: evidence of their tendency to promote drug accumulation in the brain.","authors":"William Eades, Shayan Abdolmohammadpourbonab, Linh Dinh, Bingfang Yan","doi":"10.1080/10837450.2024.2417004","DOIUrl":"10.1080/10837450.2024.2417004","url":null,"abstract":"Ionic liquids (ILs) are considered salt in liquid state, which is composed of organic cations and anions with low melting points (<100 °C). ILs have become a major scientific area with an extensive range of applications including chemistry, electrochemistry, and pharmaceutics. ILs have received great research interest in the pharmaceutical field as solvents, anti-solvents, co-solvents, and reagents in synthesis and formulation. While therapeutic ILs have been investigated for oral and trans-dermal drug delivery systems showing promising compatibility with a wide range of therapeutics, enhanced drug permeation through the skin, and cell membrane solvation to open channels to facilitate molecular passage, their potential to cross the challenging blood-brain barrier (BBB) remains an unanswered question. IL-based therapies could potentially be a game changer for improving drug delivery to cellular targets both at and across the BBB. In this review, we discuss (1) the tunable physicochemical properties of ILs; (2) the vast and various applications of ILs in the development and improvement of drug delivery systems; and (3) ILs as a potential approach for increasing drug accumulation in the brain tissue.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1065-1074"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro cellular uptake and insulin secretion studies on INS-1E cells of exendin-4-loaded self-nanoemulsifying drug delivery systems. 装载 Exendin-4 的自纳米乳化给药系统对 INS-1E 细胞的体外细胞吸收和胰岛素分泌研究。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1080/10837450.2024.2423823

Merve Çelik Tekeli, Yaprak Yalçın, Hasibe Verdi, Yeşim Aktaş, Nevin Çelebi

{"title":"In vitro cellular uptake and insulin secretion studies on INS-1E cells of exendin-4-loaded self-nanoemulsifying drug delivery systems.","authors":"Merve Çelik Tekeli, Yaprak Yalçın, Hasibe Verdi, Yeşim Aktaş, Nevin Çelebi","doi":"10.1080/10837450.2024.2423823","DOIUrl":"10.1080/10837450.2024.2423823","url":null,"abstract":"Exendin-4 (ex-4) is a peptide molecule that regulates blood glucose levels without causing hypoglycemia by providing insulin secretion from beta cells in the pancreas. Self-nanoemulsifying drug delivery systems (SNEDDS) attract attention for oral administration of therapeutic peptide/proteins because they protect therapeutic peptide/proteins from the gastric environment, reduce changes due to food effects, are easy to prepare and scale-up. Ex-4 has no commercial form that can be administered orally. In this study, the cytotoxicity, cellular uptake, and insulin secretion of ex-4 and ex-4/chymostatin (chym) SNEDDS were investigated on INS-1E rat pancreatic beta cells. The effect of ex-4 and ex-4/chym SNEDDS on cell viability in INS-1E cells increased when the dilution ratio higher. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 2.8 mM (low-dose) glucose-induced INS-1E cells 2.21-fold and 2.17-fold compared to control, respectively. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 16.7 mM (high dose) glucose-induced INS-1E cells compared to control, respectively. In cellular uptake studies, coumarin-6 solution penetrated the apical membrane of INS-1E cells and remained in the cytoplasm, while coumarin-6 loaded SNEDDS were visualized in the nuclei of the cell. These findings will likely be useful in the development of new formulations for the oral administration of peptides/proteins.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1101-1110"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanoformulated fenbendazole as an attractive approach for treating neurocysticercosis: in vitro and in vivo studies. 纳米配方芬苯达唑作为治疗神经囊虫病的一种有吸引力的方法：体外和体内研究。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-09 DOI: 10.1080/10837450.2024.2422936

Yngrid Batista da Silva, Giselle Bedogni, Guaraciara de Andrade Picanço, Jéssica Yonara de Souza, Waylla Silva Nunes, Tatiane Luiza da Costa, Geovana Batista de Campos, Lina Vargas Michelena, Claudio Javier Salomon, Marina Clare Vinaud

{"title":"Nanoformulated fenbendazole as an attractive approach for treating neurocysticercosis: in vitro and in vivo studies.","authors":"Yngrid Batista da Silva, Giselle Bedogni, Guaraciara de Andrade Picanço, Jéssica Yonara de Souza, Waylla Silva Nunes, Tatiane Luiza da Costa, Geovana Batista de Campos, Lina Vargas Michelena, Claudio Javier Salomon, Marina Clare Vinaud","doi":"10.1080/10837450.2024.2422936","DOIUrl":"10.1080/10837450.2024.2422936","url":null,"abstract":"Purpose: This work aimed to develop fenbendazole nanocrystals to evaluate their effects on the energetic metabolism of Taenia crassiceps cysticerci, following an intracranial inoculation in mice.Methods: Fenbendazole was nanoformulated by the antisolvent method using poloxamers 188 and 407 as stabilizers. The nanosuspensions were lyophilized without cryoprotectants and the nanocrystals were characterized in terms of particle size, zeta potential, and dissolution performance. The in vivo study was performed in infected animals treated with nanoformulated fenbendazole and raw drug and their metabolic impact was quantified by analyzing specific metabolites.Results: Fenbendazole samples were obtained by nanoprecipitation in > 80% yield. The average particle size of the freeze-dried samples was between 372 nm and 1600 nm. The nanosystems released a greater amount of the drug into the solution, compared to the raw drug. The in vivo studies showed that the fenbendazole-treated groups induced gluconeogenesis, partial blockage of the TCA cycle, and increased protein catabolism. As seen, the nanoformulation presented a greater effect on these parameters than the raw drug leading to remarkable modifications in the metabolism of the parasite, which in turn can influence the overall course of the infection and treatment outcomes.Conclusion: These findings suggest that nanoformulated fenbendazole may be considered a valuable approach for an effective treatment of neurocysticercosis.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1093-1100"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spray dried polymyxin B liposome for inhalation against gram-negative bacteria. 喷雾干燥多粘菌素 B 脂质体，用于吸入治疗革兰氏阴性菌。

IF 2.6 4区医学

Pharmaceutical Development and Technology Pub Date : 2024-12-01 Epub Date: 2024-11-19 DOI: 10.1080/10837450.2024.2427186

Thaddeus Harrison Gugu, Emmanuel Maduabuchi Uronnachi, Ekawat Thawithong, Teerapol Srichana

{"title":"Spray dried polymyxin B liposome for inhalation against gram-negative bacteria.","authors":"Thaddeus Harrison Gugu, Emmanuel Maduabuchi Uronnachi, Ekawat Thawithong, Teerapol Srichana","doi":"10.1080/10837450.2024.2427186","DOIUrl":"10.1080/10837450.2024.2427186","url":null,"abstract":"This study aimed to provide an alternative and effective delivery system to combat polymyxin B (PMB) toxicity and bacterial resistance through inhalation therapy. PMB was formulated as liposomal dry powder for inhalation using thin-film hydration and spray-dried methods. PMB formulations were characterized physically. The aerodynamic properties were determined using next-generation impactor (NGI). In vitro drug release was done in a phosphate buffer pH 7.4 for 2 h. Cytotoxicity was evaluated by the MTT cell viability assay. Antimicrobiological activities were done using bioassay and flow cytometry. Particle sizes of the spay-dried formulations were between 259.83 ± 9.91 and 518.73 ± 27.08 nm while the zeta potentials ranged between 3.07 ± 0.27 and 4.323 ± 0.36 mV. The Fourier-transform infrared spectroscopy shows no interaction between PMB and other excipients. Differential scanning calorimetry thermograms revealed amorphousness of the formulated powders and SEM revealed spherical PMB formulations. Similarly, mass media aerodynamic diameter results were 1.72-2.75 nm, and FPF was 25%-26%. The cumulative release of the PMB formulations was 90.3 ± 0.6% within 2 h. The killing kinetics revealed total cell death at 12 and 24 h for Pseudomonas aeruginosa and Escherichia coli, respectively. The PMB inhalation liposome showed better activity and was safe for lung-associated cell lines.","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1133-1147"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0